The fast and progressive growth of the biotechnology and pharmaceutical fields forces the development of new and powerful sensing techniques for process optimization and detection of biomolecules at very low concentrations in a fluid. To this end, in situ and real time surface adsorption studies of bio-molecules are of high interest to monitor the interactions occurring at the solid-liquid interface to eventually manipulate them towards the engineering of novel sensing devices for measuring low concentrations of the molecules in fluids. In recent years, label-free techniques such as mechanical resonators, have become an emerging and promising technology for biosensing applications, due to their small size, fast response, high sensitivity and their compatibility with integration into “lab-on-a-chip” devices. The mechanical resonators may, for example, be cantilever based. The adsorption of molecules and the biomolecular recognition on the cantilever surface may thereby be detected by monitoring cantilever bending or shifts in the resonance frequency of the cantilever.
Molecular adsorption phenomena occurring in a fluid may alternatively be detected by utilizing sensing instruments based on acoustic waves at surfaces. As an example, a quartz crystal microbalance, QCM, may be used. Commonly the adsorption of molecules is detected by determining a mass variation per unit area by measuring a change in frequency of a quartz crystal resonator of the QCM. The resonance may be shifted by the addition of a small mass due adsorption at the surface of the acoustic resonator. The QCM may be used in different fluid environments such as vacuum, gases or liquids. Frequency measurements of the quartz crystal resonator may be made to high precision and hence, mass densities down to a level of 1 ng/cm2 may be detected. In addition to or as an alternative to measuring the frequency, the dissipation, i.e. the quantity related to the energy damping in the resonator, may be measured as a resonator response.
The frequency and/or dissipation response of a resonator is, however, complex and may be influenced by many parameters such as the intrinsic material properties of the resonator, the complex relationship between an adsorption event and the resonator as well as by a change to the surrounding media of the resonator. Hence, there is a need for, not only improved detection sensitivity of mechanical resonators, but also improved reliability and robustness of the mechanical resonators.